Stem Cell Location
Any tissue or organ in stasis or undergoing repair and having a connective tissue compartment, has resident populations of mesenchymal stem cells. Organs, tissues and their associated connective tissue components assayed to date include whole embryo, whole foetus, skeletal muscle, dermis, fat, tendon, ligament, perichondrium, periosteum, heart, aorta, endocardium, myocardium, epicardium, large arteries and veins, granulation tissue, peripheral nerves, peripheral ganglia, spinal cord, dura, leptomeninges, trachea, oesophagus, stomach, small intestine, large intestine, liver, spleen, pancreas, parietal peritoneum, visceral peritoneum, parietal pleura, visceral pleura, urinary bladder, gall bladder, kidney associated connective tissues and bone marrow.
Recently, stem cells from dental pulp have been isolated by Gronthos et al. 2000, Shi et al. WO 02/07679. Sharpe (WO 01/60981) claimed the production of tooth progenitor cells from embryonic stem cells or adult stem cells or tissue culture. Moreover, Yelick and colleagues (U.S. patent application: 20020119180) claimed the method and the production of a biological tooth from third molar tooth germ (Young et al. 2002). They removed and discarded immature tooth cusps and used cells of remaining enamel and pulp organ tissues for tooth engineering.
The invention enables the skilled person to identify, separate and to build teeth like and teeth related organs and tissues by tissue engineering. The surprising advantage of the invention is the preferred use of follicle cells of wisdom teeth, which are routinely extracted in adults and children. Thus, a source of stem cells was developed which freely available even for any adult patients. In contrast to the described stem cells above, these said stem cells are differentiable into a periodontal ligament related biological membrane.
Definition of Stem Cells
A Stem Cell can replicate itself and produce cells that take on more specialized functions. The function adopted by the more differentiated daughter cells and their progeny is commonly referred to as the developmental potential, or potency, of the stem cells. Stem cells that give rise to only one type differentiated cell are termed unipotent. In common usage, the relative terms oligopotent, multipotent, and pluripotent represent an increase in the number of differentiated types from new to many or most. A totipotent cell is one that can generate the totality of cell types that can comprise the organism. In practice, these few terms poorly describe a continuum of possibilities.
The ability to form a wide variety of cell types makes pluripotent stem cells a promising resource for tissue engineering and transplantation. Through the use of enrichment, selection, expression, and sorting technologies, in vitro differentiation of stem cells will certainly contribute to future transplantation therapies.
Multipotent stem cells can be cultured from a number of foetal and adult sources. Perhaps the best known source is bone marrow, which contains both haematopoietic stem cells (Civin et al., 1984) and mesenchymal stem cells (Pittenger et al., 1999). Neural stem cells have also been cultured from the ependymal cells lining the brain ventricles (Johansson et al., 1999a). It is likely that of the many lineage-restricted stem cell populations that exist in vivo, some will be amenable to in vitro growth and analysis.
The organization of the embryo into three layers roughly corresponds to the organization of the adult, with gut on the inside, epidermis on the outside, and connective tissue in between. The endoderm is the source of the epithelial linings of the respiratory passages and gastrointestinal tract and gives rise to the pharynx, oesophagus, stomach, intestine and to many associated glands, including salivary glands, liver, pancreas and lungs. The mesoderm gives rise to smooth muscular coats, connective tissues, and vessels associated with the tissues and organs; mesoderm also forms most of the cardiovascular system and is the source of blood cells and bone marrow, the skeleton, striated muscles, and the reproductive and excretory organs. Ectoderm will form the epidermis (epidermal layer of the skin), the sense organs, and the entire nervous system, including brain, spinal cord, and all the outlying components of the nervous system.
Reserve stem cells include progenitor stem cells and pluripotent stem cells. Progenitor cells precursor stem cells, immediate stem cells, and forming or -blast cells, e.g., myoblasts, adipoblasts, chondroblasts, etc.) are lineage-committed. Unipotent stem cells will form tissues restricted to a single lineage (such as the myogenic, fibrogenic, adipogenic, chondrogenic, osteogenic lineages, etc.). Bipotent stem cells will form tissues belonging to two lineages (such as the chondro-osteogenic, adipo-fibroblastic lineages, etc.). Tripotent stem cells will form tissues belonging to three lineages (such as chondro-osteo-adipogenic lineage, etc.). Multipotent stem cells will form multiple cell types within a lineage (such as the hematopoietic lineage). Progenitor stem cells will form tissues limited to their lineage, regardless of the inductive agent that may bedded to the medium. They can remain quiescent. Lineage-committed progenitor cells are capable of self-replication but have a limited life-span (approximately 50-70 cell doublings) before programmed cell senescence occurs. They can also be stimulated by various growth factors to proliferate. If activated to differentiate, these cells require progression factors (i.e., insulin, insulin-like growth factor-1, and insulin-like growth factor-11) to stimulate phenotypic expression. In contrast, pluripotent cells are lineage-uncommitted, i.e., they are not committed to any particular tissue lineage. They can remain quiescent. They can also be stimulated.
Examples of progenitor and pluripotent stem cells from the mesodermal germ layer include the unipotent myosatellite myoblasts of muscle; the unipotent adipoblast cells of adipose tissue); the unipotent chondrogenic cells and osteogenic cells of the perichondrium and periosteum, respectively; the bipotent adipofibroblasts of adipose tissue (Vierck et al., 1996); the bipotent chondrogenic/osteogenic stem cells of marrow); the tripotent hondrogenic/osteogenic/adipogenic stem cells of marrow (Pittenger et al., 1999); the multipotent hematopoietic stem cells of marrow; the multipotent cadiogenic/hematopoietic/endotheliogenic cells of marrow; and the pluripotent mesenchymal stem cells of the connective tissues
Pluripotent mesenchymal stem cells and methods of isolation and use thereof are described in U.S. Pat. No. 5,827,735, issued Oct. 27, 1998.
Pluripotent mesenchymal stem cells can be utilized for the replacement of potentially multiple tissues of mesodermal origin (i.e., bone, cartilage, muscle, adipose tissue, vasculature, tendons, ligaments and hematopoietic), such tissues generated, for instance, ex vivo with specific morphogenetic proteins and growth factors to recreate the lost tissues. The recreated tissues would then be transplanted to repair the site of tissue loss. An alternative strategy could be to provide pluripotent stem cells, as cellular compositions or incorporated, for instance, into matrices, transplant into the area of need, and allow endogenous morphogenetic proteins and growth factors to induce the pluripotent stem cells to recreate the missing histoarchitecture of the tissue. This approach is exemplified in U.S. Pat. No. 5,903,934 which is incorporated herein in its entirety, which describes the implanting of pluripotent mesenchymal stem cells into a polymeric carrier, to provide differentiation into cartilage and/or bone at a site for cartilage repair.